title: Increased longevity of hematopoiesis in continuous marrow cultures and radiation resistance of marrow stromal and hematopoietic progenitor cells from caspase-1 homozygous recombinant-negative (knockout) mice.
abstract: OBJECTIVE
  We determined whether absence of caspase-1 altered the stress response of hematopoietic and bone marrow stromal cells in vitro.
  
  
  METHODS
  Long-term bone marrow cultures from caspase-1 -/- and control caspase-1 +/+ mice were established and the derived bone marrow stromal and interleukin-3 (Il-3)-dependent hematopoietic progenitor cell lines were evaluated for radiosensitivity.
  
  
  RESULTS
  Long-term bone marrow cultures from caspase-1 -/- mice generated hematopoietic cells for over 30 weeks in vitro, significantly longer than controls did (p=0.0018). Bone marrow stromal (mesenchymal stem cell) and Il-3-dependent hematopoietic progenitor cell lines from caspase-1-/- marrow cultures compared to caspase-1 +/+ were radioresistant (p=0.0486 and p=0.0235 respectively). Total-body irradiated caspase-1 -/- mice were not significantly radioresistant compared to controls (p=0.6542).
  
  
  CONCLUSIONS
  Caspase-1 deletion increases hematopoiesis and radioresistance of bone marrow cells in vitro.
authors.affiliation: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Epperly
authors.forename: Hebist
authors.initials: H
authors.lastname: Berhane
authors.forename: Shaonan
authors.initials: S
authors.lastname: Cao
authors.forename: Donna
authors.initials: D
authors.lastname: Shields
authors.forename: Darcy
authors.initials: D
authors.lastname: Franicola
authors.forename: Julie P
authors.initials: JP
authors.lastname: Goff
authors.forename: Xichen
authors.initials: X
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Friedlander
authors.forename: Joel S
authors.initials: JS
authors.lastname: Greenberger
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000528:radiation effects; D020170:Caspase 1 / Q000235:genetics*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D004260:DNA Repair; D060005:Genotyping Techniques; D006410:Hematopoiesis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D011836:Radiation Tolerance / Q000235:genetics*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000975:Antioxidants; D020170:Caspase 1
keywords: Caspase-1; long-term bone marrow cultures; radioresistance; radiosensitivity